DNA binding to an anticancer organo-ruthenium complex

Abstract

Because many anticancer drugs interact with DNA, the determination of their association constants to DNA is essential for quantifying their mechanisms of action. The interactions between a new ruthenium-derived compound [ruthenium(phenanthroline)(κ-C,N-(2-phenyl-pyridine)(NCMe)(2)]PF(6), called RDC11] and DNA are studied using different techniques. Fluorescent experiments are used to determine the association and dissociation constants under different salt concentrations. The binding is shown to be reversible and noncovalent. The association constants vary from 1.5 × 10(6) M(-1) to 2.9 × 10(3) M(-1) when increasing the sodium concentration from 0.1 to 200 mM. Single-molecule stretching methods are used to study the interaction of RDC with longer DNA strands (8.6 kbp home-built dimer of pBR322). The affinities of RDC with DNA under different loads are obtained using McGhee and von Hippel analysis. The affinity constant and thermodynamic parameters are in good agreement with the values found in the literature and lead to the conclusion that this molecule intercalates dsDNA.